rs4618985

Variant names:

• chr1-12611319-A-C
• rs4618985
• NM_004753.7:c.195+5835T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-12611319-A-C
• chr1-12611319-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004753.7(DHRS3):​c.195+5835T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,148 control chromosomes in the GnomAD database, including 5,629 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5629 hom., cov: 33)
• Consequence: DHRS3 NM_004753.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.968
• Publications: 8 publications found

Genes affected

DHRS3 (HGNC:17693): (dehydrogenase/reductase 3) Predicted to enable NAD-retinol dehydrogenase activity. Predicted to be involved in regulation of retinoic acid receptor signaling pathway and retinoid metabolic process. Predicted to act upstream of or within several processes, including animal organ morphogenesis; negative regulation of retinoic acid receptor signaling pathway; and regulation of ossification. Predicted to be located in endoplasmic reticulum membrane and photoreceptor outer segment membrane. Predicted to be active in lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

DHRS3 Gene-Disease associations (from GenCC):

• craniosynostosis

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ENSG00000305650 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS3	NM_004753.7	c.195+5835T>G		intron_variant	Intron 1 of 5	ENST00000616661.5	NP_004744.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHRS3	ENST00000616661.5	c.195+5835T>G		intron_variant	Intron 1 of 5	1	NM_004753.7	ENSP00000480439.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40854 AN: 152028 Hom.: 5620 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.277

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.269 AC: 40880 AN: 152148 Hom.: 5629 Cov.: 33 AF XY: 0.267 AC XY: 19854 AN XY: 74380

African (AFR) AF: 0.253 AC: 10499 AN: 41508

American (AMR) AF: 0.242 AC: 3704 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3468

East Asian (EAS) AF: 0.369 AC: 1908 AN: 5166

South Asian (SAS) AF: 0.217 AC: 1049 AN: 4824

European-Finnish (FIN) AF: 0.318 AC: 3361 AN: 10580

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18583 AN: 67992

Other (OTH) AF: 0.284 AC: 598 AN: 2106

Alfa AF: 0.271 Hom.: 4794

Bravo AF: 0.268

Asia WGS AF: 0.299 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.52
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4618985; hg19: chr1-12671324;